title: Early myoclonic epilepsy, hypertrophic cardiomyopathy and subsequently a nephrotic syndrome in a patient with CoQ10 deficiency caused by mutations in para-hydroxybenzoate-polyprenyl transferase (COQ2).
abstract: BACKGROUND
  Primary coenzyme Q10 (CoQ10) deficiencies are heterogeneous autosomal recessive disorders. CoQ2 mutations have been identified only rarely in patients. All affected individuals presented with nephrotic syndrome in the first year of life.
  
  
  METHODS
  An infant is studied with myoclonic seizures and hypertrophic cardiomyopathy in the first months of life and developed a nephrotic syndrome in a later stage.
  
  
  RESULTS
  At three weeks of age, the index patient developed myoclonic seizures. In addition, he had hypertrophic cardiomyopathy and increased CSF lactate. A skeletal muscle biopsy performed at two months of age disclosed normal activities of the oxidative phosphorylation complexes. The child was supplemented with CoQ10 (5 mg/kg/day). At the age of four months, brain MR images showed bilateral increased signal intensities in putamen and cerebral cortex. After that age, he developed massive proteinuria. The daily dose of CoQ10 was increased to 30 mg/kg. Renal biopsy showed focal segmental glomerulosclerosis. Biochemical analyses of a kidney biopsy sample revealed a severely decreased activity of succinate cytochrome c reductase [complex II + III] suggesting ubiquinone depletion. Incorporation of labelled precursors necessary for CoQ10 synthesis was significantly decreased in cultured skin fibroblasts. His condition deteriorated and he died at the age of five months. A novel homozygous mutation c.326G > A (p.Ser109Asn) was found in COQ2.
  
  
  CONCLUSIONS
  In contrast to previously reported patients with CoQ2 the proband presented with early myoclonic epilepsy, hypertrophic cardiomyopathy and only in a later stage developed a nephrotic syndrome. The phenotype of this patient enlarges the phenotypical spectrum of the multisystem infantile variant.
authors.affiliation: Department of Paediatrics, Division of Paediatric Neurology, Centre Hospitalier de Luxembourg, Rue Barblé, 4, L 1210 Luxembourg, Luxembourg. Electronic address: scalais.emmanuel@chl.lu.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Scalais
authors.forename: Ronit
authors.initials: R
authors.lastname: Chafai
authors.forename: Rudy
authors.initials: R
authors.lastname: Van Coster
authors.forename: Lutz
authors.initials: L
authors.lastname: Bindl
authors.forename: Christian
authors.initials: C
authors.lastname: Nuttin
authors.forename: Chryssa
authors.initials: C
authors.lastname: Panagiotaraki
authors.forename: Sara
authors.initials: S
authors.lastname: Seneca
authors.forename: Willy
authors.initials: W
authors.lastname: Lissens
authors.forename: Antonia
authors.initials: A
authors.lastname: Ribes
authors.forename: Caroline
authors.initials: C
authors.lastname: Geers
authors.forename: Joel
authors.initials: J
authors.lastname: Smet
authors.forename: Linda
authors.initials: L
authors.lastname: De Meirleir
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000235:genetics*; D001259:Ataxia / Q000150:complications / Q000235:genetics* / Q000473:pathology; D002312:Cardiomyopathy, Hypertrophic / Q000150:complications / Q000235:genetics* / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging; D004569:Electroencephalography; D004831:Epilepsies, Myoclonic / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007668:Kidney / Q000473:pathology / Q000648:ultrastructure; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D046529:Microscopy, Electron, Transmission; D028361:Mitochondrial Diseases / Q000150:complications / Q000235:genetics* / Q000473:pathology; D018908:Muscle Weakness / Q000150:complications / Q000235:genetics* / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D009404:Nephrotic Syndrome / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D014451:Ubiquinone / Q000172:deficiency* / Q000235:genetics
chemical_list: D014451:Ubiquinone; D019883:Alkyl and Aryl Transferases; C021386:4-hydroxybenzoate polyprenyltransferase
keywords: CoQ2 (encoding para-hydroxybenzoate-polyprenyl transferase); Early myoclonic epilepsy; Hypertrophic cardiomyopathy; Nephrotic syndrome; Primary CoQ10 deficiency